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Mutations in genes that function in maintaining genome stability, such as those involved in
DNA replication, DNA repair, or cell-cycle checkpoints, may lead to extensive genetic
alterations, leading to the so-called "mutator phenotype". In Caenorhabditis elegans, the
mutant strain dog-l(gkl0) displays such a phenotype. Molecular characterization of the strain
revealed genome-wide deletions involving a very specific type of repeat, consisting of poly-
G tracts paired with poly-C tracts ((G/C)n). Deletions have unique structural characteristics
and only occurred in roughly half of the (G/C)n tracts examined. DOG-1 contains the seven
signature motifs of a DExH-box helicase. Based on these observations, a model was
proposed in which the putative helicase DOG-1 is required for unwinding secondary
structures formed by G-rich DNA during lagging strand synthesis. In the absence of
functional DOG-1 such secondary structures may lead to deletions via an unknown
mechanism.
Because telomeric DNA is capable of forming secondary structure in vitro,
dogl(gkl0) was examined for telomere defects. To measure telomere length in C. elegans with
higher sensitivity and accuracy, a PCR-based technique, called STELA was adapted to C.
elegans thereby enabling chromosome-specific telomere length measurement from as few as
a single worm. Telomere length analysis using this technique revealed the presence of short
telomeres that were clearly distinct from the bulk telomere length distributions in different
wild-type strains. This suggests that processes other than end-replication losses and
telomerase-mediated lengthening contribute to telomere length heterogeneity in C. elegans.
An increased frequency of such short outlying telomeres was observed in the telomerase
mutant trt-1, indicating that besides replicative loss, telomerase is also required for
preventing large scale loss of telomeric DNA. Analysis of telomere length in dog-l(gkl0)
using STELA showed no significant shortening of average telomere length or increased
frequency of short telomeres. Therefore, DOG-1 appeared to be required specifically for the
maintenance of (G/C)n tracts within the genome.